In search of sex-related mediators of affective illness

Abstract

Sex differences in the rates of affective disorders have been recognized for decades. Studies of physiologic sex-related differences in animals and humans, however, have generally yielded little in terms of explaining these differences. Furthermore, the significance of these findings is difficult to interpret given the dynamic, integrative, and highly context-dependent nature of human physiology. In this article, we provide an overview of the current literature on sex differences as they relate to mood disorders, organizing existing findings into five levels at which sex differences conceivably influence physiology relevant to affective states. These levels include the following: brain structure, network connectivity, signal transduction, transcription/translation, and epigenesis. We then evaluate the importance and limitations of this body of work, as well as offer perspectives on the future of research into sex differences. In creating this overview, we attempt to bring perspective to a body of research that is complex, poorly synthesized, and far from complete, as well as provide a theoretical framework for thinking about the role that sex differences ultimately play in affective regulation. Despite the overall gaps regarding both the underlying pathogenesis of affective illness and the role of sex-related factors in the development of affective disorders, it is evident that sex should be considered as an important contributor to alterations in neural function giving rise to susceptibility to and expression of depression.

Understanding the Links among Maternal Diet, Myelination, and Depression: Preclinical and Clinical Overview

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Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study

“…From our data, it seems that men could be less susceptible to psychological symptoms like anxiety, PTSD or insomnia. Previous research has identified several domains that could explain this gender differences between men and women in psychological symptoms, including brain structure, network connectivity, signal transduction, transcription/translation, epigenetic changes, and hormonal changes during life course 40 , 41 .…”

Sex‐specific behavioral, neurobiological, and cardiovascular responses to chronic social stress in mice

“…The risk of stress‐dependent psychopathology differs markedly between the sexes, with women more than twice as likely to develop depression and anxiety disorders (Hantsoo & Epperson, 2017; Kessler, 1997; Olff, 2017; Verma et al, 2011), and displaying more severe symptoms (de Graaf et al, 2002). Distinct (in some cases opposing) neurobiological changes are reported in men and women with stress‐related major depressive disorder (MDD), supporting unique mechanisms of disease in males and females (Seney et al, 2018; Sikes‐Keilp & Rubinow, 2021). Experimental animal studies also identify opposing neurobiological and behavioral responses to social stress in females and males (Oliver et al, 2020; Rivera‐Irizarry et al, 2020).…”